02314nas a2200373   4500000000100000008004100001100001400042700001700056700002000073700001900093700001600112700001700128700002000145700001400165700002200179700001900201700001100220700001600231700002200247700002000269700001800289700002000307700001900327700001600346700001600362700001700378700001500395700002100410700002000431700001800451245007600469520138100545022001401926       2018                            d1 aGroup GEM1 aThomas Nancy1 aEdmiston Sharon1 aKanetsky Peter1 aBusam Klaus1 aKricker Anne1 aArmstrong Bruce1 aCust Anne1 aAnton-Culver Hoda1 aGruber Stephen1 aLuo Li1 aOrlow Irene1 aGallagher Richard1 aZanetti Roberto1 aRosso Stefano1 aSacchetto Lidia1 aParrish Eloise1 aHao Honglin1 aGibbs David1 aOllila David1 aBegg Colin1 aBerwick Marianne1 aConway Kathleen1 aDwyer Terence00aInherited Genetic Variants Associated with Melanoma BRAF/NRAS Subtypes.3 a<p>BRAF and NRAS mutations arise early in melanoma development but their associations with low-penetrance melanoma susceptibility loci remain unknown. In the Genes, Environment and Melanoma (GEM) Study, 1223 European-origin participants had their incident invasive primary melanomas screened for BRAF/NRAS mutations and germline DNA genotyped for 47 single-nucleotide polymorphisms (SNPs) identified as low-penetrant melanoma risk variants. We used multinomial logistic regression to simultaneously examine each SNP's relationship to BRAF V600E, BRAF V600K, BRAF other, and NRAS+ relative to BRAF-/NRAS- melanoma adjusted for study features. IRF4 rs12203592*T was associated with BRAF V600E (OR = 0.59, 95% CI = 0.43-0.79) and V600K (OR = 0.65, 95% CI = 0.41-1.03), but not BRAF other or NRAS+ melanoma. A global test of etiologic heterogeneity (P = 0.001) passed false discovery (P = 0.0026). PLA2G6 rs132985*T was associated with BRAF V600E (OR = 1.32, 95% CI = 1.05-1.67) and BRAF other (OR = 1.82, 95% CI = 1.11-2.98), but not BRAF V600K or NRAS+ melanoma. The test for etiologic heterogeneity (P) was 0.005. The IRF4 rs12203592 associations were slightly attenuated after adjustment for melanoma-risk phenotypes. The PLA2G6 rs132985 associations were independent of phenotypes. IRF4 and PLA2G6 inherited genotypes may influence melanoma BRAF/NRAS subtype development.</p>  a1523-1747